Scientists begin melanoma vaccine tests

WASHINGTON Ä Among the thousands of Americans who get melanoma every year, only a few have a natural immune reaction that keeps this deadliest of skin cancers from coming back.

Now scientists are bottling that protection, testing hundreds of melanoma patients with an experimental vaccine they hope will keep the killer at bay.

"When people recur from melanoma, they're extremely likely to die," explained Dr. Robert Israel of Progenics Pharmaceuticals, which manufactures the vaccine. "We're looking to keep them from recurring, and ultimately to survive."

It's too early to predict how well the vaccine called gm2 will work. While initial experiments suggest it is potent, doctors only recently began Phase III testing - the biggest hurdle any medicine must pass - with 850 patients.

But scientists once frustrated by repeatedly failing cancer vaccines now are cautiously excited.

New immune system discoveries have led to "approaches that were not possible even five years ago," said vaccine hunter Dr. Steven Rosenberg of the National Cancer Institute. His agency is funding the Progenics experiment and a trial of a competing melanoma vaccine - Ribi ImmunoChem's Melacine.

"We're beginning to understand for the first time the molecular basis of how the immune system of a patient responds to their cancer," Rosenberg said. "It's a very exciting time."

Melanoma strikes about 40,300 Americans every year, and kills over 7,000. Sun exposure is the main cause, and the most at risk are people who had even one bad sunburn as a child.

Surgery often cures early melanoma. But up to 30 percent of early- to intermediate-stage patients will suffer a recurrence in a few years - because the surgery missed tiny cells waiting to grow into new, even deadlier tumors.

The idea is for these patients' immune systems to catch and kill the leftover melanoma cells before they become a threat. Dr. Philip Livingston of Memorial Sloan-Kettering Cancer Center discovered that a few of his patients - about one in 20 - could do that naturally.

Their immune systems developed antibodies to gm2, a substance on the surface of melanoma cells. The antibodies track down this so-called antigen and then kill its host cells. So Livingston purified gm2 to give to patients whose immune systems don't react to the antigen on their own.

An early study of 122 patients, unveiled last month at Australia's World Conference on Melanoma, found those vaccinated with gm2 remained cancer-free for 33 months vs. 17 months for unvaccinated patients.

The study was too small to be statistically significant. Still, after Livingston made some changes to further boost the vaccine's potency, the results prompted NCI to finance the 850-patient trial that could settle the issue by 1999.

Ribi ImmunoChem is trying a different attack, a vaccine made from pieces of melanoma cells grown in a laboratory. Such vaccines are often considered less potent than more targeted vaccines. But Melacine has an advantage: it provides many more melanoma antigens for the immune system to hunt, explained Ribi vice president Kenneth von Eschen.

In the NCI-run trial of 689 patients, Ribi should know in late 1998 whether Melacine effectively prevents melanoma from recurring.

But Ribi also wants to sell Melacine to treat the sickest melanoma patients, not just as a possible prevention.

In a final study of late-stage melanoma, 70 Melacine patients lived 11 months while another 70 who got standard chemotherapy lived 12.4 months - a difference too small to be significant.

But Melacine caused only one serious side effect compared to 86 chemotherapy caused, so Ribi this fall will seek Food and Drug Administration approval to sell Melacine as a safer alternative for advanced melanoma.

For patients still hoping to keep melanoma at bay, however, Livingston acknowledges his first vaccine needs improving. First, nobody knows how long patients need vaccinations. And his naturally protected patients seem to make antibodies indefinitely, while vaccinated patients lose the antibodies weeks after their shots stop.

Nevertheless, any success with melanoma, a cancer fairly easy to study, could prompt vaccines against other killers like breast cancer, whose cell surfaces also bear a variety of antigens.

"Everything we see from experiments ... so far suggests antibodies should be able to make a difference," Livingston said. "This trial will answer that question."